Applying cryopreserved amniotic membrane following intravitreal injection

Dry eye disease (DED) was first defined in 1995. Since then, its definition has been revised to include a complex, multifactorial aetiology that includes hyperosmolarity, tear film instability, ocular surface inflammation and damage and neurosensory abnormalities.¹

A characteristic feature of DED is disruption of the epithelial barrier at the ocular surface. Exposure of the corneal epithelium to increased osmolarity promotes inflammation, causing a cascade of events leading to apoptosis. Neurogenic chronic inflammation and disease severity worsen with inflammation induced by tear film instability and hyperosmolarity.²

Cryopreserved amniotic membrane (CAM) is a promising therapy for corneal nerve regeneration and accelerated recovery of ocular surface health in patients with DED. CAM helps to improve a number of problems, such as pain, corneal staining, overall dry eye signs and symptoms (eg, discomfort, visual disturbances), corneal nerve density and corneal sensitivity.³

CAM is a biologic corneal bandage designed to treat damaged corneas by creating an environment for regenerative healing. Prokera is the only US Food and Drug Administration-cleared CAM product and supports the corneal healing process without harmful adverse effects. With early intervention, its CryoTek preservation method maintains full biologic components to help rapidly restore the cornea’s own healing capabilities.⁴

Ocular surface disease

Ocular surface disease (OSD) is an underrecognized and underappreciated problem that is difficult to treat. It often affects the cornea, and treating it is not in the typical retina specialist’s skill set. Anti-VEGF therapy has become the standard of care for treating macular oedema and a range of other retinal diseases. However, intravitreal (IVT) injections require proper access and antiseptic techniques, which can cause corneal problems.

Betadine is the biggest culprit. Although it has a good track record of being a great antimicrobial and antiseptic, it can cause corneal toxicity, especially with repeated use. When patients have post-injection pain, it’s typically related to ocular surface disruption due to the betadine application. Although patients complain about the pain of the IVT shot at first, this quickly dissipates, and it’s common for patients to call in even after a few hours following injection, when they suddenly notice incredible pain (usually from the betadine) in their eye.

I have made some modifications in my practice. Rather than using a lot of betadine all over the eye, I use a more targeted approach. In some patients, for example, I will soak a Q-tip in betadine and place it over the affected area.

OSD symptoms are rarelydue to nonadherence. Instead, when patients read, watch TV, drive a car, or use a computer, they stare; and when they stare, they don’t blink, which exacerbates OSD symptoms. This eventually leads to DED and OSD. Patients who undergo IVT therapy are more likely to have blurry vision due to their retinal pathology. It is human nature to stare when you don’t see well.

Treatment algorithm

When patients present with dry eyes, I tend to start them on artificial tears. If a patient shows persistent signs and symptoms despite using tears frequently, then I use punctal plugs. If the patient is having dry eye problems and needs IVT shots, this process may exacerbate their symptoms. If the patient is very symptomatic, I would potentially give the patient a trial of Prokera or anther amniotic membrane. I explain that it may be uncomfortable for a few days but it’s going to give them between 9 and 12 months of relief. Although this isn’t a perfect solution, we do not have an approved alternative to betadine at this time, so we’re trying to make the best of the situation.

I prefer this algorithm because we start with trying therapies that are least invasive and most cost-effective first, and then if these do not work, we move our way up. This process also increases adherence in patients who need injections to maintain their vision.

Benefits of CAM therapy

I like CAM because I know that, when I put it on, it is centred on the cornea. The problem with other amniotic membranes is that they may fold or not fitwell, requiring a lot of logistics, which makes the process more complicated. Amniotic membranes are not something I do on a daily basis as a retina specialist, so using CAM makes the process much easier, even if it’s abit more uncomfortable for some patients.CAM is easy and fast, and I know I’ve done it right. Retina clinicians are busy, so anything to make the process easier with the least amount of hassle is better for my patients and I.

CAM is for patients who continue to complain about their OSD signs and who are symptomatic, even though they’re using drops and plugs. These are high-need, corneal-sensitive patients. CAM won’t change the IVT therapy patients undergo, but it will make it better.

Although we are not looking to replace the general ophthalmologist or cornea specialist in managing DED, once patients start with retina specialists, most don’t see their regular ophthalmologist routinely. Retina specialists should understand that what they do can contribute to worsening dry eye. At minimum, we can recommend artificial tears for all our patients, and if they have persistent signs and symptoms, we might continue moving up the algorithm I described. Of course, conferring with their referring eye care provider is very important, as different providers have varying views on who should manage these patients’ DED.

Retina specialists need to be more aware of OSD and what patients are going through. They also need to know that giving IVT shots can have unintended consequences. One of the secondary benefits of managing DED is that retina specialists will end up with higher patient adherence. One long-term issue with current therapies is that patient adherence wanes over time. Patients don’t want to come into the doctor’s office several times. If the process of getting an IVT injection is more comfortable, then we will have better patient adherence andbetter outcomes, which make our patients, their family and our community better.

Michael A. Singer, MD

E: msinger11@me.com

Michael A. Singer, MD, is a clinical professor of ophthalmology at The University of Texas Health Science Center in San Antonio, and director of clinical research at Medical Center Ophthalmology.

References

1. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017;15(3):276-283.doi:10.1016/j.jtos.2017.05.008

2. Bron AJ, de Paiva CS, Chauhan SK, et al. TFOS DEWS II pathophysiology report. Ocul Surf. 2017;15(3):438-510.doi:10.1016/j.jtos.2017.05.011

3. John T, Tighe S, Sheha H, et al. Corneal nerve regeneration after self-retained cryopreserved amniotic membrane in dry eye disease. J Ophthalmol. 2017;2017:6404918.doi:10.1155/2017/6404918

4. Prokera. BioTissue. Accessed May 19, 2022. https://www.biotissue.com/prokera/